Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study

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• 作者：Prof Patrick Marcellin ; MD^a ; ^{patrick.marcellin@bjn.aphp.fr} ; Prof Edward Gane ; MD^b ; Prof Maria Buti ; MD^c ; Prof Nezam Afdhal ; MD^d ; Prof William Sievert ; MD^e ; Prof Ira M Jacobson ; MD^f ; Prof Mary Kay Washington ; MD^g ; Prof George Germanidis ; MD^h ; John F Flaherty ; PharmDⁱ ; Raul Aguilar Schall ; PhDⁱ ; Jeffrey D Bornstein ; MDⁱ ; Kathryn M Kitrinos ; PhDⁱ ; G Mani Subramanian ; MDⁱ ; John G McHutchison ; MDⁱ ; Prof E Jenny Heathcote ; MBBS^j
• 刊名：The Lancet
• 出版年：2013
• 出版时间：9-15 February, 2013
• 年：2013
• 卷：381
• 期：9865
• 页码：468-475
• 全文大小：241 K

文摘

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Summary

Background

Whether long-term suppression of replication of hepatitis B virus (HBV) has any beneficial effect on regression of advanced liver fibrosis associated with chronic HBV infection remains unclear. We aimed to assess the effects on fibrosis and cirrhosis of at least 5 years' treatment with tenofovir disoproxil fumarate (DF) in chronic HBV infection.

Methods

After 48 weeks of randomised double-blind comparison (trials and ) of tenofovir DF with adefovir dipivoxil, participants (positive or negative for HBeAg) were eligible to enter a 7-year study of open-label tenofovir DF treatment, with a pre-specified repeat liver biopsy at week 240. We assessed histological improvement (¡Ý2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis) and regression of fibrosis (¡Ý1 unit decrease by Ishak scoring system).

Findings

Of 641 patients who received randomised treatment, 585 (91 % ) entered the open-label phase, and 489 (76 % ) completed 240 weeks. 348 patients (54 % ) had biopsy results at both baseline and week 240. 304 (87 % ) of the 348 had histological improvement, and 176 (51 % ) had regression of fibrosis at week 240 (p<0¡¤0001). Of the 96 (28 % ) patients with cirrhosis (Ishak score 5 or 6) at baseline, 71 (74 % ) no longer had cirrhosis (¡Ý1 unit decrease in score), whereas three of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 (p<0¡¤0001). Virological breakthrough occurred infrequently and was not due to resistance to tenofovir DF. The safety profile was favourable: 91 (16 % ) patients had adverse events but only nine patients had serious events related to the study drug.

Interpretation

In patients with chronic HBV infection, up to 5 years of treatment with tenofovir DF was safe and effective. Long-term suppression of HBV can lead to regression of fibrosis and cirrhosis.

Funding

Gilead Sciences.